改良气管插管法在小鼠心肌梗死模型制备中的应用

目的：小鼠心肌梗死模型制备中采用改良气管插管方法,提高模型制备成功率。方法：小切口暴露小鼠气管,直视下进行经口气管插管,左冠状动脉前降支结扎制备心肌梗死模型,观察、记录小鼠心脏颜色和心电图、术后14d存活情况和心肌组织病理学变化。结果：采用改良气管插管,成功完成40只小鼠心肌梗死模型制作,均可见冠状动脉结扎后,心室前壁颜色变暗,心电图Ⅱ导联ST段明显抬高。除去手术过程中意外死亡,术后14d存活27只,心肌梗死小鼠实际成活率达到87．1％。开胸后,肉眼可见模型组小鼠左室心腔明显扩大,心室壁变薄;病理切片HE染色,镜下可见心肌纤维断裂溶解,心肌细胞坏死,大量炎性细胞浸润。结论：在小鼠心肌梗死模型制备中,采用改良气管插管法,操作简单、易行、创伤小,模型制备成功率高。     

Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction

Summary Both cell therapy and angiogenic growth factor gene therapy have been applied to animal studies and clinical trials. Little is known about the direct comparison between cell therapy and angiogenic growth factor gene therapy. The goal of this study was to compare the effects of human bone marrow-derived mesenchymal stem cells (hMSCs) transplantation and injection of angiogenic growth factor genes in a model of acute myocardial infarction in mice. The hMSCs were obtained from adult human bone marrow and expanded in vitro. The purity and characteristics of hMSCs were identified by flow cytometry and immunophenotyping. Immediately after ligation of the left anterior descending coronary artery in male severe combined immunodeficient (SCID) mice, culture-expanded hMSCs or angiogenic growth factor genes were injected intramuscularly at the left anterior free wall. The engrafted hMSCs were positive for cardiac marker, desmin. Infarct size was significantly smaller in the hMSCs-treated group than in the angiopoietin-1 (Ang-1) or vascular endothelial growth factor (VEGF)-treated group at day 28 after infarction. hMSCs transplantation was better in decreasing left ventricular end-diastolic dimension and increasing fractional shortening than Ang1 or VEGF gene therapy. Capillary density was markedly increased after hMSCs transplantation than Ang1 and VEGF gene therapy. In conclusion, intramyocardial transplantation of hMSCs improves cardiac function after acute myocardial infarction through enhancement of angiogenesis and myogenesis in the ischemic myocardium. hMSCs are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction. Transplantation of MSCs may become the future therapy for acute myocardial infarction for myocardial regeneration.     

Cigarette smoking might weaken the prognostic significance of cytochrome P450 2C19*2 polymorphism in acute myocardial infarction patients

Prognostic significance of cytochrome P450 2C19*2 polymorphism in acute myocardial infarction is still not well investigated. The aim of the study was to determine the relationship between the genetic polymorphism and the outcome of the acute myocardial infarction patients, and to further clarify the impact of smoking on such relationship. Six hundred acute myocardial infarction patients were enrolled. All of them provided blood samples and underwent clopidogrel treatment. The genetic polymorphism was determined by polymerase chain reaction–restriction fragment length polymorphism analysis, and the platelet function was assessed using conventional aggregometry. Of the included patients, 287 carried GG wild‐type genotypes, 225 carried GA genotypes and 88 carried AA genotypes. The platelet aggregation rate was significantly elevated in the AA genotype patients, mainly in the non‐smoking patients (P < 0.001) and the former‐smoking patients (P < 0.001). During 5‐year follow‐up period, after adjusted for multiple confounding factors, AA genotypes were associated with the increase in 5‐year mortalities in the non‐smoking patients [OR: 7.06, 95% confidence interval (CI): 2.16–11.49] and the former‐smoking patients (OR: 4.38, 95% CI: 1.05–9.40), but not in the current‐smoking patients (OR: 1.12, 95% CI: 0.60–2.31). In conclusion, the study suggested a potential role of P450 2C19*2 polymorphism as a prognostic indicator in acute myocardial infarction patients. We had also obtained some evidence that current smoking might weaken the prognostic significance of the genetic polymorphism in patients.     

IGFBP‐4 enhances VEGF‐induced angiogenesis in a mouse model of myocardial infarction

Vascular endothelial growth factor (VEGF) is a well‐known angiogenic factor, however its ability in promoting therapeutic angiogenesis following myocardial infarction (MI) is limited. Here, we aimed to investigate whether dual treatment with insulin‐like growth factor binding protein‐4 (IGFBP‐4), an agent that protects against early oxidative damage, can be effective in enhancing the therapeutic effect of VEGF following MI. Combined treatment with IGFBP‐4 enhanced VEGF‐induced angiogenesis and prevented cell damage via enhancing the expression of a key angiogenic factor angiopoietin‐1. Dual treatment with the two agents synergistically decreased cardiac fibrosis markers collagen‐I and collagen‐III following MI. Importantly, while the protective action of IGFBP‐4 occurs at an early stage of ischemic injury, the action of VEGF occurs at a later stage, at the onset angiogenesis. Our findings demonstrate that VEGF treatment alone is often not enough to protect against oxidative stress and promote post‐ischemic angiogenesis, whereas the combined treatment with IGFBP4 and VEGF can utilize the dual roles of these agents to effectively protect against ischemic and oxidative injury, and promote angiogenesis. These findings provide important insights into the roles of these agents in the clinical setting, and suggest new strategies in the treatment of ischemic heart disease.     

CRP velocity and short-term mortality in ST segment elevation myocardial infarction

Context: There is a known association between C-reactive protein (CRP) levels and adverse outcomes in patients presenting with ST-elevation myocardial infarction (STEMI). The optimal time frame to measure CRP for risk stratification is not known.

Objective: The aim of the current study was to evaluate the relation between the change in CRP velocity (CRPv) and 30-d mortality among STEMI patients.

Material and methods: We included consecutive patients with a diagnosis of STEMI who presented to Tel-Aviv Medical Center between 2008 and 2014 and had their CRP measured with a wide range assay (wr-CRP) at least twice during the 24?h after admission. CRPv was defined as the change in wr-CRP concentration (mg/l) divided by the change in time (in hours) between the two measurements.

Results: The study population comprised of 492 patients, mean age was 62?±?14, 80% were male. CRPv was significantly higher among patients who died within 30 d of admission (1.42?mg/l versus 0.18?mg/l, p?<?0.001). In a multivariate regression model adjusted to multiple confounders, CRPv was independently associated with 30-d mortality (OR 1.39, 95% CI: 1.20–1.62, p?<?0.001).

Conclusion: CRPv might be an independent and rapidly measurable biomarker for short-term mortality in patients presenting with STEMI.     

Effect of alcohol drinking and cigarette smoking on neutrophil functions in adults

In recent years, the effects of smoking and excessive alcohol consumption on immune function have been studied, due to a high prevalence of infection or cancer in heavy drinkers, and the combination of smoking and drinking was considered to be a carcinogenic risk. However, the effect of smoking and drinking on systemic immune function has yet to be clearly understood. In this study, we investigated neutrophil functions (reactive oxygen species (ROS) productive activity, phagocytic ability and serum opsonic activity) and their relationship with alcohol consumption or amount of smoking. In total there were 731 male and female adult subjects who participated in the Iwaki Health Promotion Project in 2005. Multiple regression analysis showed a trend of increased ROS production in male subjects and a statistically significant decrease was observed in phagocytic activity caused by smoking in female subjects. In other words, oxidative stress caused by smoking in male subjects may be involved in ROS production from neutrophils. Decreased phagocytic activity of neutrophils caused by smoking suggests that host defense functions were impaired in female subjects. A relationship between neutrophil functions and the amount of alcohol consumption was not observed. Copyright © 2011 John Wiley & Sons, Ltd.     

Curcumin ameliorated myocardial infarction by inhibition of cardiotoxicity in the rat model

Cardiovascular diseases are the main cause of death globally. Many attempts have been done to ameliorate the pathological changes after the occurrence of myocardial infarction. Curcumin is touted as a polyphenol phytocompound with appropriate cardioprotective properties. In this study, the therapeutic effect of curcumin was investigated on acute myocardial infarction in the model of rats. Rats were classified into four groups; control, isoproterenol hydrochloride (ISO) (100 mg/kbw), curcumin (50 mg/kbw), and curcumin plus ISO treatment groups. After 9-day administration of curcumin, levels of lactate dehydrogenase (LDH), creatine kinase (CK), and cardiac troponin I (cTnI) were determined. Superoxide dismutase (SOD) and malondialdehyde (MDA) contents were measured to investigate the oxidative status in infarct rats received curcumin. By using H & E staining, tissue inflammation was performed. Masson’s trichrome staining was conducted to show cardiac remodeling and collagen deposition. The number of apoptotic cells was determined by using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Data showed the serum decrease of LDH, CK, and cTnI in infarct rats after curcumin intake compared to the rats given (ISO) ( P < 0.05). Curcumin was found to reduce oxidative status by reducing SOD and MDA contents ( P < 0.05). Gross and microscopic examinations revealed that the decrease of infarct area, inflammation response and collagen deposition in rats given ISO plus curcumin ( P < 0.05). We noted the superior effect of curcumin to reduce the number of apoptotic cardiomyocytes after 9 days. Data point the cardioprotective effect of curcumin to diminish the complication of infarction by the reduction of cell necrosis and apoptosis in a rat model of experimental infarction.     

End stage renal disease‐induced hypercalcemia may promote aortic valve calcification via Annexin VI enrichment of valve interstitial cell derived‐matrix vesicles

Patients with end‐stage renal disease (ESRD) have elevated circulating calcium (Ca) and phosphate (Pi), and exhibit accelerated progression of calcific aortic valve disease (CAVD). We hypothesized that matrix vesicles (MVs) initiate the calcification process in CAVD. Ca induced rat valve interstitial cells (VICs) calcification at 4.5 mM (16.4‐fold; p < 0.05) whereas Pi treatment alone had no effect. Ca (2.7 mM) and Pi (2.5 mM) synergistically induced calcium deposition (10.8‐fold; p < 0.001) in VICs. Ca treatment increased the mRNA of the osteogenic markers Msx2, Runx2, and Alpl (p < 0.01). MVs were harvested by ultracentrifugation from VICs cultured with control or calcification media (containing 2.7 mM Ca and 2.5 mM Pi) for 16 hr. Proteomics analysis revealed the marked enrichment of exosomal proteins, including CD9, CD63, LAMP‐1, and LAMP‐2 and a concomitant up‐regulation of the Annexin family of calcium‐binding proteins. Of particular note Annexin VI was shown to be enriched in calcifying VIC‐derived MVs (51.9‐fold; p < 0.05). Through bioinformatic analysis using Ingenuity Pathway Analysis (IPA), the up‐regulation of canonical signaling pathways relevant to cardiovascular function were identified in calcifying VIC‐derived MVs, including aldosterone, Rho kinase, and metal binding. Further studies using human calcified valve tissue revealed the co‐localization of Annexin VI with areas of MVs in the extracellular matrix by transmission electron microscopy (TEM). Together these findings highlight a critical role for VIC‐derived MVs in CAVD. Furthermore, we identify calcium as a key driver of aortic valve calcification, which may directly underpin the increased susceptibility of ESRD patients to accelerated development of CAVD.     

Aging impairs human bone marrow function and cardiac repair following myocardial infarction in a humanized chimeric mouse

Ventricular remodeling following myocardial infarction (MI) is a major cause of heart failure, a condition prevalent in older individuals. Following MI, immune cells are mobilized to the myocardium from peripheral lymphoid organs and play an active role in orchestrating repair. While the effect of aging on mouse bone marrow (BM) has been studied, less is known about how aging affects human BM cells and their ability to regulate repair processes. In this study, we investigate the effect aging has on human BM cell responses post‐MI using a humanized chimeric mouse model. BM samples were collected from middle aged (mean age 56.4 ± 0.97) and old (mean age 72.7 ± 0.59) patients undergoing cardiac surgery, CD34^+/− cells were isolated, and NOD‐scid‐IL2rγ^null (NSG) mice were reconstituted. Three months following reconstitution, the animals were examined at baseline or subjected to coronary artery ligation (MI). Younger patient cells exhibited greater repopulation capacity in the BM, blood, and spleen as well as greater lymphoid cell production. Following MI, CD34⁺ cell age impacted donor and host cellular responses. Mice reconstituted with younger CD34⁺ cells exhibited greater human CD45⁺ recruitment to the heart compared to mice reconstituted with old cells. Increased cellular responses were primarily driven by T‐cell recruitment, and these changes corresponded with greater human IFNy levels and reduced mouse IL‐1β in the heart. Age‐dependent changes in BM function led to significantly lower survival, increased infarct expansion, impaired host cell responses, and reduced function by 4w post‐MI. In contrast, younger CD34⁺ cells helped to limit remodeling and preserve function post‐MI.     

Interactions of the eNOS and ACE genes and cigarette smoking in chronic obstructive pulmonary disease

BackgroundChronic obstructive pulmonary disease (COPD) is a complex disorder with unexplained heritability. Interactions of genetic and environmental factors are thought to be crucial in COPD. So, we aim to examine interactions of the endothelial nitric oxide synthase (eNOS) and angiotensin converting enzyme (ACE) genes and cigarette smoking in COPD.MethodsThe eNOS G 894T and ACE ID variants were analyzed in 122 COPD patients and 200 controls from Serbia. The effect of the variants on COPD was assessed by logistic regression. Interactions between eNOS, ACE and cigarette smoking in COPD were evaluated using a case-control model. Interaction between the genes was analyzed in silico.ResultsNo effect of the eNOS G 894T and ACE ID variants on COPD was found in our study. Gene-gene interaction between the eN OS T T and A CE D was identified (p=0.033) in COPD. The interaction is realized within the complex network of biochemical pathways. Gene-environment interactions between the eNOS T and cigarette smoking (p=0.013), and the ACE II and cigarette smoking (p=0.009) were detected in COPD in our study.ConclusionsThis is the first research to reveal interactions of the eNOS and ACE genes and cigarette smoking in COPD progressing our understanding of COPD heritability and contributing to the development of appropriate treatments     

慢性吸烟大鼠气道平滑肌大电导的钙激活钾通道和Kv1.5表达的变化

复制大鼠的慢性吸烟模型,采用气道反应性的测定、HE染色、免疫组织化学染色、原位杂交和免疫印迹实验等方法,观察吸烟对大鼠支气管平滑肌大电导的钙激活的钾通道(BKca)和电压依赖性延迟整流钾通道Kv1．5蛋白和mRNA表达的影响,以阐明吸烟引起的气道高反应性发病机制中钾通道表达变化的作用。结果显示：(1)慢性吸烟可降低大鼠大气道和小气道BKca和Kv1．5蛋白和mRNA表达;(2)大气道BKca的降低程度大于Kv1．5,小气道BKca和Kv1．5的降低程度无明显差异：(3)吸烟对全肺组织BKca和Kv1．5的蛋白表达无明显影响。上述结果提示,慢性吸烟可下调大鼠气道平滑肌钾通道BKca和Kv1．5的表达水平,是导致气道高反应的机制之一。     

The effect of immune cell-derived exosomes in the cardiac tissue repair after myocardial infarction: Molecular mechanisms and pre-clinical evidence

After a myocardial infarction (MI), the inflammatory responses are induced and assist to repair ischaemic injury and restore tissue integrity, but excessive inflammatory processes promote abnormal cardiac remodelling and progress towards heart failure. Thus, a timely resolution of inflammation and a firmly regulated balance between regulatory and inflammatory mechanisms can be helpful. Molecular- and cellular-based approaches modulating immune response post-MI have emerged as a promising therapeutic strategy. Exosomes are essential mediators of cell-to-cell communications, which are effective in modulating immune responses and immune cells following MI, improving the repair process of infarcted myocardium and maintaining ventricular function via the crosstalk among immune cells or between immune cells and myocardial cells. The present review aimed to seek the role of immune cell-secreted exosomes in infarcted myocardium post-MI, together with mechanisms behind their repairing impact on the damaged myocardium. The exosomes we focus on are secreted by classic immune cells including macrophages, dendritic cells, regulatory T cells and CD4⁺ T cells; however, further research is demanded to determine the role of exosomes secreted by other immune cells, such as B cells, neutrophils and mast cells, in infarcted myocardium after MI. This knowledge can assist in the development of future therapeutic strategies, which may benefit MI patients.     

大鼠心肌梗死模型建立方法选择及心电图表现

目的探讨构建心肌梗死模型的大鼠左冠状动脉结扎位置及心电图特点。方法 SD大鼠经麻醉后,气管切开插管及连通呼吸机,打开左侧胸腔后分别在距离左心耳尖端约2 mm水平处(低位结扎组)与在距主动脉根部约3 mm处(高位结扎组)结扎左冠动脉,假手术组除不结扎冠脉外步骤同低位结扎组,术前术后分别行心电图检查,且4周后取出心脏行病理学检查及测定心肌梗死面积。结果高位结扎组大鼠心肌梗死面积约55.5%,总存活率13.3%;低位结扎组大鼠心肌梗死面积约36.2%,总存活率66.7%;假手术组大鼠无心肌梗死,存活率100%。大鼠体表心电图在非心肌梗死者QRS-T波群呈成"M"型波,在心肌梗死者R波与T波融合成高大的帐篷状单波,无明显ST段。4周后心肌组织形态学特点符合心肌梗死的病理改变。结论距大鼠主动脉根部约3 mm结扎左冠状动脉,不能满足实验需要;距离左心耳尖端约2 mm水平结扎左冠状动脉,能满足实验需要;大鼠的体表心电图无明显ST段。     

Overexpression of sema3a in myocardial infarction border zone decreases vulnerability of ventricular tachycardia post‐myocardial infarction in rats

The expression of the chemorepellent Sema3a is inversely related to sympathetic innervation. We investigated whether overexpression of Sema3a in the myocardial infarction (MI) border zone could attenuate sympathetic hyper‐innervation and decrease the vulnerability to malignant ventricular tachyarrhythmia (VT) in rats. Survived MI rats were randomized to phosphate buffered saline (PBS, n = 12); mock lentivirus (MLV, n = 13) and lentivirus‐mediated overexpression of Sema3a (SLV, n = 13) groups. Sham‐operated rats served as control group (CON, n = 20). Cardiac function and electrophysiological study (PES) were performed at 1 week later. Blood and tissue samples were collected for histological analysis, epinephrine (EPI), growth‐associated factor 43 (GAP43) and tyrosine hydroxylase (TH) measurements. QTc intervals were significantly shorter in SLV group than in PBS and MLV groups (168.6 ± 7.8 vs. 178.1 ± 9.5 and 180.9 ± 8.2 ms, all P < 0.01). Inducibility of VT by PES was significantly lower in the SLV group [30.8% (4/13)] than in PBS [66.7% (8/12)] and MLV [61.5% (8/13)] groups (P < 0.05). mRNA and protein expressions of Sema3a were significantly higher and the protein expression of GAP43 and TH was significantly lower at 7 days after transduction in SLV group compared with PBS, MLV and CON groups. Myocardial EPI in the border zone was also significantly lower in SLV group than in PBS and MLV group (8.73 ± 1.30 vs. 11.94 ± 1.71 and 12.24 ± 1.54 μg/g protein, P < 0.001). Overexpression of Sema3a in MI border zone could reduce the inducibility of ventricular arrhythmias by reducing sympathetic hyper‐reinnervation after infarction.     

间歇运动对心梗大鼠心肌氧化应激和炎症的影响及其机制

目的:探讨间歇运动激活心肌梗死(MI)大鼠SIRT1-Nox4-ROS通路抑制心脏氧化应激和炎症的作用.方法:选取雄性SD大鼠30只,随机分为假手术对照(C)组,心肌梗死(MI)组和心梗+间歇运动(ME)组,每组10只.MI组采用心脏左冠状动脉前降支(LAD)结扎法,建立MI模型.C组大鼠实施假手术,ME组大鼠在MI手...     

Reduced oxidative activity of circulating neutrophils in patients after myocardial infarction

Circulating neutrophils isolated from patients 3–4 h after a myocardial infarction produced less $ {\rm O}\frac{ \cdot }{{\rm 2}} $ compared with controls, when stimulated with phorbol myrystate acetate or formyl-methionine-leucine-phenylalanine. Three days after the infraction the $ {\rm O}\frac{ \cdot }{{\rm 2}} $ generation elicited by both stimuli further decreased markedly. Seven and 15 days after infarction the $ {\rm O}\frac{ \cdot }{{\rm 2}} $ stimulated production was only slightly lower than or similar to the control values. The neutrophils of infarcted patients showed an augmented latency period before $ {\rm O}\frac{ \cdot }{{\rm 2}} $ production compared with controls in response to exogenous stimuli, particularly three days after infarction. Electron microscopy revealed that the neutrophils isolated from the infarcted patients displayed signs of cell exhaustion with few alterations of the plasma membranes when stimulated with phorbol ester. In contrast, control neutrophils displayed alterations of the plasma membranes characteristic of active neutrophils. The results of this study indicate that the circulating neutrophils appear exhausted and functionally inhibited immediately after myocardial infarction.     

Invasive surgery reduces infarct size and preserves cardiac function in a porcine model of myocardial infarction

Reperfusion injury following myocardial infarction (MI) increases infarct size (IS) and deteriorates cardiac function. Cardioprotective strategies in large animal MI models often failed in clinical trials, suggesting translational failure. Experimentally, MI is induced artificially and the effect of the experimental procedures may influence outcome and thus clinical applicability. The aim of this study was to investigate if invasive surgery, as in the common open chest MI model affects IS and cardiac function. Twenty female landrace pigs were subjected to MI by transluminal balloon occlusion. In 10 of 20 pigs, balloon occlusion was preceded by invasive surgery (medial sternotomy). After 72 hrs, pigs were subjected to echocardiography and Evans blue/triphenyl tetrazoliumchloride double staining to determine IS and area at risk. Quantification of IS showed a significant IS reduction in the open chest group compared to the closed chest group (IS versus area at risk: 50.9 ± 5.4% versus 69.9 ± 3.4%, P = 0.007). End systolic LV volume and LV ejection fraction measured by echocardiography at follow‐up differed significantly between both groups (51 ± 5 ml versus 65 ± 3 ml, P = 0.033; 47.5 ± 2.6% versus 38.8 ± 1.2%, P = 0.005). The inflammatory response in the damaged myocardium did not differ between groups. This study indicates that invasive surgery reduces IS and preserves cardiac function in a porcine MI model. Future studies need to elucidate the effect of infarct induction technique on the efficacy of pharmacological therapies in large animal cardioprotection studies.     

Ferroptosis in myocardial infarction: not a marker but a maker

Identification of effective cardiac biomarkers and therapeutic targets for myocardial infarction (MI) will play an important role in early diagnosis and improving prognosis. Ferroptosis, a cell death process driven by cellular metabolism and iron-dependent lipid peroxidation, has been implicated in diseases such as ischaemic organ damage, cancer and neurological diseases. Its modulators were involved in transferrin receptor, iron chelator, clock protein ARNTL, etc. Its mechanisms included the inhibition of system X_C⁻, diminished GPX4 activity, change of mitochondrial voltage-dependent anion channels and rising intracellular reactive oxygen species level. Further, the inhibitors of apoptosis, pyroptosis and autophagy did not prevent the occurrence of ferroptosis, but iron chelating agents and antioxidants could inhibit it. Noticeably, ferroptosis is an important pattern of cardiomyocyte death in the infarcted area, which may play a vital role in support of the myocardial pathological process of heart disease. However, the molecular mechanism of ferroptosis in the pathogenesis and the development of MI is not clear. Therefore, a greater depth of exploration of the mechanism of ferroptosis and its inhibitors will undoubtedly improve the pathological process of MI, which may be expected to identify ferroptosis as novel diagnostic and therapeutic targets of MI.     

High plasma thiocyanate levels are associated with enhanced myeloperoxidase-induced thiol oxidation and long-term survival in subjects following a first myocardial infarction

Abstract

Elevated levels of myeloperoxidase (MPO) are associated with poor cardiovascular outcomes. MPO uses H₂O₂ to generate oxidants including HOCl and HOSCN, from chloride and thiocyanate (SCN^?) ions, respectively. SCN^? is the preferred substrate. Elevation of this anion decreases HOCl generation and increases HOSCN formation, a thiol-specific oxidant. Such changes are of potential relevance to people with elevated SCN^? levels, such as smokers. In this retrospective study, we examined whether elevated plasma MPO and SCN^? levels increased thiol oxidation as a result of increased HOSCN formation, and impacted on long-term survival in 176 subjects (74 non-smokers, 46 smokers, and 56 previous smokers) hospitalized after a first myocardial infarction. Plasma thiols were not significantly altered in smokers compared to non-smokers or past smokers. However, significant positive correlations were detected between SCN^? levels and MPO-induced thiol loss in the total population (r = 0.19, P = 0.020) and smokers alone (r = 0.58, P < 0.0001). Twelve-year all-cause mortality data indicate that above median MPO is significantly associated with higher mortality, but below-median MPO and above-median SCN^? results in increased survival, compared to below-median SCN^?. Cox proportional hazard analysis showed a significant decrease in mortality for each 1 μM increase in SCN^? (0.991; P = 0.040). Subject age was, as expected, a strong predictor of subject survival. Overall these data suggest that subjects with below-median MPO and above-median SCN^? have better long-term survival, and that elevated plasma levels of SCN^? might be protective in at least some populations.